Successful Primate Trial Offers Hope
For Malaria Vaccine Candidate
WESTPORT, Apr 07 (Reuters) - A 19-kDa fragment of the major merozoite surface antigen-1 (MSP1) from Plasmodium cynomolgi, a primate analog of P. vivax, elicits high antimalarial antibody titers and extended protection against blood-stage malaria infection in primates.
Dr. Kamini Mendis, of the University of Colombo in Sri Lanka, and colleagues there and in France report in the April issue of Infection and Immunity their success with this leading malaria vaccine candidate in a primate trial.
They vaccinated three groups of three animals each with two different C-terminal fragments of MSP1--42-kDa or 19-kDa--either alone or in combination. Three doses were administered subcutaneously at 4-week intervals and included complete and incomplete Freund's adjuvants. Two additional groups of three animals each received either normal saline or no vaccine.
Four weeks after immunization, the scientists inoculated the animals with P. cynomolgi parasites isolated from a donor monkey. All six control monkeys became infected, with patency lasting at least 44 days. By contrast, all of the immunized monkeys showed high antibody titers against the antigens and only one of nine was not protected against challenge.
The remaining animals showed "...either no parasitemia at all or transient parasitemias which were patent for only 1 or 2 days," according to Dr. Mendis and others. Moreover, monkeys immunized with the 19-kDa fragment showed sustained protection against a second challenge 6 months later.
"Protection as complete as that elicited in this trial has rarely, if ever, been achieved in primates with a recombinant subunit malaria vaccine against blood stage parasites," the authors report.
They point out that if the protection conferred by MSP1 vaccines is dependent upon the high antibody titers elicited, the next "...challenge ahead for preparation of an analogous human P. vivax vaccine will be to replace the potent Freund's adjuvant." Preliminary data suggest that comparable antibody titers can be obtained "...by using alum, which is the only adjuvant currently acceptable for human use."
Dr. Mendis and colleagues noted that the sustained protection observed in p19 vaccinees to a second challenge could have been due to the first immunization or, more likely, "...boosted by a minimal exposure to parasites during the first challenge." In other words, protection against homologous Plasmodium strains "...might be induced by a single complete blood stage infection." Such a finding "...implies that vaccine-induced immunity could be boosted by natural infection, a feature which could be of considerable importance for the deployment of an MSP1 p19-based vaccine in malaria-endemic areas," the scientists propose.
"These results are now being confirmed in a trial with larger numbers of animals," the researchers say. Dr. Mendis and associates stress that "...the real relevance of the results reported here will by determined only by clinical trials with the P. vivax MSP1 recombinant analogs."
Infect Immun 1998;66:1500-1506.
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